Tissue Issues: A Deep Dive into Cutaneous Connective Tissue Disease

Summary

Podcast Summary: Derms on Drugs

Episode: "Tissue Issues: A Deep Dive into Cutaneous Connective Tissue Disease"

Date: March 6, 2026
Host(s): Matt Zirwas, Laura Ferris, Tim Patton
Guest: Dr. Lauren Graham (University of Alabama, Birmingham)

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Overview

This episode offers a dynamic, in-depth exploration of cutaneous connective tissue diseases, focusing especially on cutaneous lupus erythematosus (CLE) and dermatomyositis (DM). The hosts, joined by special guest and connective tissue expert Dr. Lauren Graham, dissect the latest research, evolving therapies, diagnostic challenges, disease scoring, and more. The tone is lively, fun, slightly irreverent, and loaded with useful clinical pearls for dermatology professionals.

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Key Discussion Points and Insights

1. Dr. Graham’s Path to Connective Tissue Disease (01:13)

• Dr. Graham shares her journey: from an MD/PhD in collagen research at UAB, to a residency at Northwestern, sparking her interest through exposure to combined clinics (lupus, scleroderma, psoriasis/psoriatic arthritis).
• Quote: “I did my PhD work on collagen regulation… tried a derm rotation in third year and really liked it… fell in love with connective tissue disease.” (01:25–03:02)

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2. Review of Ducravacitinib in Cutaneous Lupus (04:22)

Paper: Autoimmunity Reviews: “Ducravacitinib: Superior efficacy and safety in Cutaneous Lupus erythematosus compared to various biologics and small molecules: Systematic review and meta-analysis.”
Presenter: Dr. Laura Ferris

Core Findings

• Ducravacitinib (a TIC2 inhibitor, not FDA-approved for CLE) appears more effective than ustekinumab and baricitinib, based on odds of achieving CLASI-50 improvement.
  • Odds ratios: Ducravacitinib 8.28, lidifilimab 2.54, anafrolumab 2.25 (vs placebo) (08:18).
• Only one true phase 2 RCT with 218 SLE patients (multiple dosing arms) informs ducravacitinib's strong showing; overall study quality varies.
• CLASI (Cutaneous Lupus Area and Severity Index)—A score of 50% improvement (“CLASI-50”) defines clinical response, but meaningfulness is relative to baseline severity.
  • “If they’re really bad, 50 percent better is a decent amount. The standard is that 50% change is clinically significant.” —Dr. Graham (09:27)

Safety

• No higher overall adverse event rates for ducravacitinib vs placebo.
• Baricitinib showed higher SAEs.

Industry Insight

• Matt: “It’s like they (BMS) don’t want to make any money… they never did a lupus study, never did atopic derm. Who’s running their pipeline?” (15:12)

Clinical Takeaways

• Ducravacitinib is used off-label by some (difficult approval, occasional success), “We’re in an exciting time for skin lupus, still.” —Dr. Graham (20:39)
• “We have so much need for something that’s easy to use and relatively safe.” —Dr. Ferris (16:14)
• Hydroxychloroquine sometimes triggers psoriatic dermatitis, a nuance in coverage/diagnosis.

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3. Litifilimab for Cutaneous Lupus: The LILAC Study (21:52)

Paper: Morola et al. “Litifilimab efficacy on skin outcomes in cutaneous lupus erythematosus: Phase 2 LILAC study”

Mechanism and Background

• Anti-BDCA2 monoclonal antibody, it inhibits PDCs and downstream type 1 interferon signaling; promising for CLE.

Results

• Fast Results: Statistically significant improvement at Week 4 for CLASI-50 at top dose; 70% on best dose vs 17% on placebo.
• Placebo group improvement often reflects better compliance with background therapy during trials, per Dr. Patton and Dr. Graham.
• Works especially well for higher baseline disease activity.

Safety & Practice Insights

• No alarming safety signals for litifilimab; less concern for viral infections compared to anafrolumab.
• “It works fast, and they saw a difference at week 4, which is exciting.” —Dr. Graham (25:40)
• Subjective improvement: Physician global impression aligns with how dermatologists practice (“Are you better, worse, or the same?”), even though it’s subjective.

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4. Anafrolumab in SLE/CLE (39:00)

• Good real-world results: Used increasingly in SLE patients with poorly controlled skin disease; “The first thing we’re giving them is anafrolumab. And it works really well and it works fast.” —Dr. Graham (40:00)
• Infectious risk (particularly herpes zoster); zoster vaccination recommended before use.
• Subcutaneous formulation in EU (approved December 2025), with trials ongoing in the US.

Clinical Pearl

• Use of systemic lupus diagnosis can facilitate access to advanced therapies for severe CLE.

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5. Diagnostic Pearls and New Developments

• No major new diagnostic labs for lupus or DM—clinical evaluation is still paramount.
• Dr. Graham: “The biggest thing is just recognizing the difference between lupus and dermatomyositis… Do a good clinical exam. Make sure it’s not dermato.” (46:25)

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6. Dermatomyositis: New and Old Treatments (48:30)

• Therapies: IVIG (only FDA-approved), methotrexate, mycophenolate, increasing off-label JAK inhibitor usage (tofacitinib, upadacitinib); repicitinib (TIC2/JAK1) in phase 3 trials.
• Oral Roflumilast: Emerging as a promising therapy for cutaneous DM (anecdotal use by Dr. Zirwas).
• IVIG: Good for skin, not perfect—may be less effective for complete clearance.
• Cancer Screening: Follow new guidelines—comprehensive annual screening for at least first 3 years after DM diagnosis.
• Myositis Antibody Panels: Utility is there, but false negatives are common and treatment shouldn’t wait for results.

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7. Clinical Pattern Recognition in Dermatomyositis (56:42)

• Teaching pearls: Examine recalcitrant scalp erythema, violaceous upper back/arms, Gottron's papules (knuckles); heliotrope is overrated.
• “The upper back and outer arms, a little bit violaceousy—that’s my bells ringing for DM.” —Dr. Zirwas (57:29)

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Notable Quotes & Memorable Moments

• “My job is to be like our listeners who didn’t look anything up ahead of time, so I gotta ask the questions they would ask. Plus it’s a good excuse for me to do less work.” – Matt (11:08)
• “If you're describing yourself as classy, you're not.” – Matt, playing on the CLASI acronym (12:07)
• “We used to have nothing—literally it was Plaquenil, maybe quinacrine, methotrexate, and that was it.” – Dr. Zirwas on historic lupus management (21:15)
• “Nothing is FDA-approved for cutaneous lupus as a standalone disease, and as derms, we see that fairly frequently.” – Dr. Patton (22:12)
• “I do all cancer screening yearly for three years” after DM diagnosis – Dr. Graham (53:26)
• “Heliotrope is one of the most overhyped signs—I identify it after I know they have dermato.” – Matt (58:17)
• “If anything, this tells us we need to own cutaneous lupus… if we do get things FDA approved, dermatologists really need to be empowered.” – Dr. Graham (45:28)

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Timestamps for Important Segments

• Dr. Graham’s background & training: 01:13–03:02
• Ducravacitinib review, CLASI-50 explanation: 04:22–10:49
• Meta-analysis results (odds ratios): 08:18–12:07
• Litifilimab (LILAC study), trial setup: 21:52–30:02
• Discussion of disease scoring (CLASI, physician's global impression): 29:51–34:47
• Anafrolumab in SLE/CLE: 39:00–44:14
• Accessing advanced therapies via SLE diagnosis: 44:14–45:28
• New developments in diagnosis: 46:25–46:41
• Dermatomyositis therapies (IVIG, JAKs, repicitinib): 48:51–52:18
• Malignancy screening in DM: 53:05–54:15
• Dermatomyositis antibody panels and diagnosis: 54:58–56:39
• Clinical pattern recognition for DM: 57:29–58:43

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Trivia & Historical Nuggets (59:32–65:27)

• First use of antimalarials for SLE noted in World War II soldiers on malaria prophylaxis.
• ANA testing uses the HeLa cell line rather than the original Hep-2.
• Gottron (of Gottron papules fame) took over after a Jewish dermatologist (Jessner, of Jessner's peel) was ousted during Nazi era.

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Conclusion

The episode is equal parts clinical review and comedic banter, offering:

• Up-to-the-minute discussion on the latest therapeutics for cutaneous lupus and dermatomyositis (Ducravacitinib, litifilimab, anafrolumab, IVIG, oral refulmilast).
• Real-world insights from an expert with nuanced, honest discussion of what actually works in clinic.
• Practical pearls on scoring, diagnosis, and recognizing disease patterns.
• Engaging anecdotes and discussion on the path to new drug approvals, real-world barriers, and employing "creative" diagnoses to unlock needed therapies.

Perfect for dermatology clinicians eager for lively, actionable updates in connective tissue disease.

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“We’re in an exciting time for skin lupus... I hope dermatologists are empowered to take care of these patients.”
— Dr. Lauren Graham (45:33)

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Transcript

[A]

Welcome to season two of Derms on Drugs, a video podcast brought to you by Scholars of Medicine. The best educational platform dermatology, and provided at no cost to medical providers. Terms on Drugs is where cutting edge term meets hit or miss comedy. I'm Matt Ziers from Docs Dermatology and each week I'm joined by my residency buddies, Dr. Laura Farish from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh. And we use our 60 years of combined derm experience to discuss, debate and dissect the hottest topics in dermatology. It is everything you need to know to be on the cutting edge of dermatology, and you'll hopefully have some fun listening. New episodes drop every Friday on Scholars of Medicine, Apple Podcasts, Spotify and other major podcast platforms. And there is a video component that should be available wherever you get your podcast. It has the key figures and tables from the articles we talk about. So this week we are doing one of our Deep Dive episodes that I'm so excited about because it is a topic that I do not follow at all. So I will be learning lots. This week we're going to be doing cutaneous connective tissue disease, and we've got Dr. Lauren Graham from the University of Alabama, Birmingham. Dr. Graham, great to have you on the show.

[B]

Hi. Thank you for having me. I'm excited to be here.

[A]

Oh, that's. So what, so what is your. How did you end up being a connective tissue disease person? Like, what was your, what was kind of your pathway to where'd you do residency and all that? How'd you pick this, all that stuff?

[B]

It was a long path. So I did the MD, PhD program at UAB at University of Alabama at Birmingham. Had no idea what I wanted to do. Dermatology was not on my radar and ended up doing my PhD work on collagen regulation. And so then I said, oh, well, what. What could be relevant for that? And actually anything could, right? Fibrosis, sclerosis, scarring, wound healing.

[A]

Well, wait, the first thing we have, first thing we have to ask right away, like, which collagen should we all be taking to get rid of our wrinkles? I mean, you should be a billionaire at this point.

[B]

I know my family gets mad that I don't do cosmetic dermatology and, and help them look, have more collagen in their face. And so then I fell into dermatology. I tried it. I did a rotation in third year med school and really liked it and then did a two plus two program. I trained At Northwestern University in Chicago. And did you. Two plus two.

[A]

When did you graduate? How long ago?

[B]

How long ago? I graduated in 2015, so.

[A]

2015 from residency? Yeah. Yeah. So you've been out like 10 years.

[B]

Yep.

[A]

So you got to work with Amy Pow, who was. Was there a connective tissue disease person at Northwestern where you were there?

[C]

There was.

[B]

There's. There's actually a few. And they actually had some. Several combined clinics, which is where I really got to start working with rheumatologists. They had a psoriasis psoriatic arthritis clinic. They had a Morpheus scleroderma clinic, which is what I really got into. And so then we had another person who was really focused on lupus. So I got really good training there and that's when I kind of fell in love with connective tissue disease.

[A]

We. We got phenomenal connective tissue disease training at that pit. So they have a incredible room department. And there was like one of the world experts for scleroderm, a guy named Tom Medzker, who I assume he has to be dead by now.

[D]

Retired.

[A]

Retired at a minimum. So he, he was fan. There was a. Yeah. A lupus person, a dramato person, a scleroderma person. Just. Yeah. Really? They were. They were great people. Are. Is. What was her name? Manzi? Is she still around? Does she still have amazing hair? Because she always had.

[B]

She does have.

[D]

Very nice.

[C]

I went over to Ahn and do. I stopped talking to her.

[D]

She's chair of medicine at the competing health system across the town. And fun fact, married to my PhD advisor.

[A]

Oh, wow.

[B]

Small world.

[A]

Okay.

[D]

Yes.

[B]

Oh, and fun fact, I went to the other school across town for undergrad.

[A]

Wait, which other school?

[B]

Oh, yeah, I went to Duke for Underground.

[D]

I have heard of that school.

[B]

Yeah.

[D]

Wow.

[B]

Hey, it's a big week for basketball coming up. Go Go World.

[D]

It is, it is. I know. Good thing we get to be friends now because I don't know what's going to happen come Saturday. Lauren.

[C]

We'll see.

[A]

All right, well, let's. Let's go ahead and get into it. So, Dr. Ferris.

[C]

What?

[A]

You've got our first paper. What are you talking about?

[D]

Yeah, so. So this paper I picked, it's in autoimmunity reviews and it is Ducravacitinib. Superior efficacy and safety in Cutaneous Lupus erythematosis compared to various biologics and small molecules. Systematic review and meta analysis. So, you know, this was kind of interesting because as we all know, Ducrabacitinib is not FDA approved. To treat cutaneous lupus. But it's a tough. It's a tough disease. And so what they did was they looked to see Ducrabacitinib. And I had seen some clinical trials, sort of early data showing that it works in cutaneous lupus. And maybe it's a little more promising there than it is, you know, A. So TIC2 for psoriasis. So, you know, so what they did was they compared it up to the other drugs like anafromab, lidopilumab, And I hope Dr. Graham's going to, you know, fill us in on pronunciation, ustakin, etc. Did I do it? Okay, good. All right, good. So, okay, so what this paper did was it looked at 53 different studies. Now, they weren't all like randomized control trials. 21 of them were. Some of them were observational series, Some of them were even just case reports. And they looked at novel systemic therapies for CLE or SLE with active skin disease. And they really looked at all studies that used the clazi score. And the primary outcome that they looked at was clazi 50, which is at least a 50% improvement in the clazy A. So just to like the. A little quick and dirty about, about that. The clazy A is the cutaneous lupus area and severity index, and the A is the active part. Right. So we all know discoid lupus. You can get a patient's disease totally quiet, but their skin's not going to necessarily look normal. You're going to have the damage part of it too. So you're really just looking at activity. Okay, so what were sort of the main players that they looked at? Ducravacitinib, oral selective TIC2 inhibitor, anafrolumab. And how does that work? It binds to the interferon alpha receptor 1 and it blocks type 1 interferon signaling, lidofilimab. And that is an anti BDCA2 monoclonal antibody. So what does that do? It binds to plasma cytoid dendritic cells and decreases type 1 interferon activity. Baricitinib, we all know. JAK1, 2 inhibitor, ustekinumab, IL2003 12 inhibitor. And then they also looked at some other data on things that were like Belimumab, which is a B cell activating factor drug, Ritux.

[A]

Why would a B. Why would a B cell activating drug work like it seems? Seems like you want the opposite.

[D]

So lupus itself, I'm sorry, it is an anti B cell activating anti bath, so belimumab, so it decreases B cell activity. So they looked at some other things, like other JAK1 inhibitors, but these were sort of the ones that, you know, that they focused on now. Important to think about. So DIB is like, what made the title, right? Like, this is, look, it works. But there was really only one phase 2 randomized control trial in patients with SLE with active skin disease consisting of 91 patients. So, I'm sorry, 91 patients on 218 patients of whom, like 91 were on the high dose, 93 were on. No, 91 on low dose, 93 on mid dose, 89 on high dose, and then 45 on placebo. So this is not. It's a big study for lupus218, but it's not like tons and tons of patients. So just keep in mind, only one of the studies actually had ducrabisit.

[A]

Okay.

[D]

Okay. So they used. So they looked. Then they looked across, you know, multiple different studies. So what did they find? So, first of all, they looked at, like, who's more likely to get you to Clasi 50? And so looking at. And they used placebo as their. Like, one for looking at odds ratios. So ducrabacitinib at an odds ratio of 8.28 versus placebo. Lidifilimab, it was 2.54, and anafrolumab, it was 2.25. So that's how many more times likely that drug was than placebo to get patients to reach a class A.

[A]

So I often get in trouble when I interrupt Dr. Faris, but I have a question I have to get into right now because I have no sense of this. So classes. So, Dr. Graham, classy 50. Like, I know very well in my head, like, okay, this is what easy, easy 75 looks like. This is what easy 90 looks like. This is what passy 90 looks like. Like, whatever is classy 50. Like, hey, the patient's gonna be like, I am a lot better, but I still is like. Or is classy 50? Like, I'm okay. Like, what's. How good is classy 50?

[B]

I think that's a good question. And I think it. It depends on how bad they are to start. Cause it's 50% better. Right?

[A]

Okay, that makes sense.

[B]

You know, if they're really bad, 50% better is a good, decent amount. The standard is that thought that a 50% change is clinically significant. And currently people are working on getting an actual number for the class each so that, you know, we can have an absolute number for improvement. Which makes a clinical signal. Yeah, but the activity is based on erythema and scale.

[A]

Okay.

[B]

So you can have. You can go from really red and really scaly to, you know, less red and less scalable scaly. And you could get to a classic with and with.

[A]

So with dle, it doesn't take scar. Obviously it shouldn't take scarring into account because that's not going to get better.

[B]

That's the damage part.

[A]

Does it take depigmentation into account at all? Because that's.

[B]

Yes, but again, that's on the damage side.

[A]

Okay.

[B]

Erythema and scale and hypertrophy are on the activity side. And then dispigmentation, atrophy, those kind of things are on the damage side.

[A]

So there's the classy and the klutzy. Like is. What's the. What's.

[B]

So they're both part of the classy. So there's classy A, which stands for classy. A is activity, and then there's. And then there's the D for the damage part.

[A]

Okay. All right.

[B]

They usually look at the A part, which is the activity.

[A]

Okay. So the A is mainly erythema and scaling. Okay. All right. Got it. All right, Dr. Ferris, I. You. I give you the blessing. You can go on again.

[D]

Thank you so much.

[C]

Zero time looking up anything related to lupus. He just brings it up during the.

[A]

My job is to be like our listeners who, like, they didn't look anything up ahead of time, so I gotta ask the questions. They would ask. Plus, it's a good excuse for me to do less work.

[D]

That's good.

[B]

That works.

[D]

No, I like the idea of like a low. Like, what's a clinically meaningful clasi score? So, like, I do a lot of psoriasis. We say like, oh, you know, what percent, like, treat to target. Like, what's a pazi? You know, a BSA less than 1% or a PASI score less than. I think it's like 2. So it would be great to have a classy score if you said if your class is less than 2, that means you really have barely significant disease, whereas 50% of horrible is still kind of bad. Right.

[B]

And most of the studies require a classy of at least 10 to even get into trials. But, you know, you can have 20s and in the 30s, you can. It divides each area of the body into sections and you count those separately.

[A]

So since we're going to keep saying the word classy, I've got to just put this out there that the, you know, the best way to know if someone is classy or not is if they describe themselves as classy. The minute you describe yourself as I'm a classy. No, you are not. That is you. You can't. It's kind of like you can't call yourself humble. You can't call yourself classy.

[B]

It just.

[A]

It doesn't work.

[D]

It doesn't work.

[B]

Okay.

[D]

Words to live by. Nothing to do with lupus, but thank you.

[B]

All right,

[D]

so the other like little pearls here was. They said, well, okay, does do crab is sit. Okay. What works better than like used to kidney mab and basically like all Ducrabicitinib, lidifilimab, anifrolumab, all were significantly better than Ustekinumab. And interestingly, baricitinib came out significantly less effective than ducravacitinib and lidophilumab. Like its odds ratios were 0.11 or 0.37.

[A]

We know what dose they use because like berries got such a do like from 2mg to 8mg is like berry seems like it'd be a hard one to. To meta. Analysize. Yeah, because depends completely on the dose.

[D]

I think when they're doing those odds ratios, like usually those trials have a dose ranging because these are all going to be like phase two studies. So I don't know that we have that answer, but I'll see if I can.

[B]

I think they use 2mg and 4mg. 2 and 4.

[A]

That doesn't work at all.

[B]

Okay.

[D]

Oh, yeah, you're right. There is the little plot. Okay, so yes, that, that is, that is true. Okay, so then the other thing that they looked at was safety. And basically they didn't really see overall adverse event rate differences and they did not for serious adverse event rates. They really did not see a big difference for like ducravacitinib or aniflob or lidopilumab versus placebo. They did show a higher odds ratios of serious adverse events for baricitinib versus placebo.

[A]

Okay, Faris, can I, can I ask you another, another question now?

[D]

Nitpicking.

[A]

This one I don't, I don't think is too nitpicky. Why are you BMs?

[D]

I am classy.

[C]

You're still into the trap. Thank you.

[D]

Thank you for asking.

[A]

So bms, like, it seems I don't know the BMS people. I haven't worked at all with the BMS people. They're the ones who make Ducrevacitinib Right. What's wrong with them? They are like, this is a good drug, and it has done terribly in psoriasis. It would be a great atopic derm drug. They never did any studies. It would be like, if they had done a lupus study and gotten a lupus approval. Like, it's like, they don't want to make any money. I don't. I don't understand. Like, have you worked with them at all? Do you know, like, why they are so incompetent?

[B]

I have.

[D]

Yeah. So I'm not BMS saying you are incompetent. That is Matt virus, Just in case you're listening. No, but I. So I think it's just a bigger market. Right. Like, they're not a big skin disease company. Traditionally. If you're like, what do you. It's like, why do you rob banks? That's where the money is.

[B]

Why do you test your drug? And psoriasis.

[D]

That's where the volume and is. I. That is my guess. It is interesting because I actually think this is a better lupus drug than it is a psoriasis drug. Right.

[A]

It looks like it.

[D]

And it's just a more saturated market.

[A]

So, yeah, whoever the consultants are that these companies hire, they need to stop hiring them and hire me instead. I would. I would have told these people on day one, like, you're out of your minds. Like, yeah, okay.

[B]

Yes.

[A]

It's a huge market. Oh, my God. You could make a trillion dollars if you can get everybody to give up all the drugs they love already, which.

[D]

That already works.

[A]

Good luck with that.

[D]

Yeah.

[B]

I think they are moving to concentrate more in lupus.

[A]

Okay, good.

[D]

I do. Yes, I have heard that, too. And I think that would be great because it's also just, like, an area where we have so much need for something that's easy for us to use and relatively safe and, you know, so, you know, so it's obviously not yet approved for SLE or clean, and it's not in the EULAR 2023 guidelines or anything like that. But, you know, I think it's something that is. That looks promising. And interestingly, it is, you know, probably looks a little more promising than some of the drugs like Anafro Lab, Anifrolia, MAB, and litophilumab that we're actually pursuing.

[A]

I'm not gonna try to say.

[D]

And, yeah, don't try to do that. So, you know, quick, like, strengths. This is a good meta analysis that included 21 randomized controlled trials and also did try to put in, like, Case reports and case series. You know, downsides. One phase two study that was actually in SLE patients where they had a, a classy as an outcome. So they did look at patients who had cutaneous disease. There's really not many of these were head to head studies. So you know, it's better to do from my limited understanding, metalysis better if you've got a bunch of head to head and you know, drug to placebo, you know, comparisons. So you know, other things that were interesting. So I did take a quick like literally five minute review of that 2022 paper that, that sle d kravisitinib paper. And so they did look at the doses of 3 milligra bid. 6 milligrams bid are 12 milligrams a day. So keep in mind like those are not. We have one, a 6 milligram once a day pill of Decravisitinib. So we don't really have that, that dose that they looked at available and they did add it to like standard therapy. And why like you'd be like, well so what? Who cares if it's not that dose? More is better. What's actually kind of interesting is that when you look at their data, it actually looks like patients did better on that 3 milligram bid dose. Like the 12 milligram a day dose was actually a little bit worse. So good news is that's 6 milligrams a day and that's what we have, you know, available to us. The baseline clase, so in the patients in that study was around 8. And as Dr. Graham just said, for most dedicated lupus studies you have to be 10 going in. And then if you look at the CLASI 50 response, it was like 70% of patients on the 3 bid, which was the best responder versus 16.7% on placebo. So that's a pretty big difference. So I thought that that was interesting. And then the other thing, and I'm going to give Dr. Patton credit because he has far more time on his hands than I do. He actually went on to. And just for those of you who don't know, he doesn't work most of the Mondays, so which is. So he was able, he even had a whole day to look at this.

[C]

That was just between us. But okay.

[A]

And for, for those not watching, those not watching on video, he's got kind of a, that part got kind of a deer look going on today. I like that. Like that outfit. Patent.

[C]

That's nice.

[A]

Black. Yeah, it's good.

[D]

Yeah. So, but There is. There was actually data on clinical trials.gov for a dedicated ducrabicitinib and cutaneous lupus study. And so thank you. As much as I like to make fun of you for actually pulling this out of this unpublished data out. So what they did show was that if they looked at the mean change in Clazi A in this study, placebo was about 27% reduction in Clasi A. And the two doses of Ducravacitinib, 3mg bid and 6mg bid were both pretty similar at about 49% change. And the percent of patients reaching classy 50, 21% placebo, 60% 3mg bid dosing, and 54% at 6mg bid dosing. So there is some data. So I'm kind of excited. I think that this will be a good, you know, option for lupus patients. So, Dr. Graham, are you ever using this? Are you using Ducravacitinib off label in your cutaneous lupus?

[B]

We've done it a couple times. As you mentioned, it's off label, so we have a hard time getting it approved. But when they've failed everything else, we can get it. Or if you actually, you know, hydroxychloroquine is a risk factor for psoriasis. So sometimes these patients do have psoriatic dermatitis. So that sometimes can make it a little easier to get because they really do have some psoriatic areas. So I've had. I like it. I've had success with it, but I've had success with the other ones, too. I think we're in an exciting time for skin lupus still.

[D]

Still.

[B]

We still have room to go, but it's better than it was five, 10 years ago.

[A]

I remember, like, as a resident, whenever we used to manage, like, a fair amount of this, I still can remember some of those patients were, like, pretty much you had, like, plaquenil chloroquine. Like, I'm. I was doing a lot of plaque chloroquine plus quinacrine, because. Right. It was supposed to be more potent that way. And putting it together with methotrexate and. But, you know, like, stuff that if I. If I tried to do any of that now, I would be like, oh, my God, I'm so terrified. I'm gonna put.

[B]

I mean, we're still having to do it, unfortunately, but less so, which is nice.

[A]

Okay. Okay. All right, Patton, what do you. What do you got over there?

[C]

All right. My deep dive paper was. Is based on the exciting announcement made by the FDA January this year granting breakthrough therapy designation to Litophilimab. They're making litophilimab great again. That, that and measles. Yeah. The article is titled Little Philo about efficacy on skin outcomes in cutaneous lupus erythematosis in the phase two Lilac study by Worth and Morola et al. In the intro, the authors point out medications like hydroxychloroquine, methotrexate, corticosteroids, mycophenolate, quote, fail to provide satisfactory efficacy and have some toxicity concerns. Sure, you can see how Biogen is downselling all these drugs that we use to treat lupus. Nothing is FDA approved to treat cutaneous lupus as a standalone disease. And as germs, we see that fairly frequently. Interferon 1 seems to be playing a significant role in cutaneous lupus. Hence the efficacy of anafrolumab, an antibody which blocks type 1 interferon receptors. Where does that come from? Plasma cytoid dendritic cells or PDCs, as cool immunologists probably say. I would know. I'm a cool dermatologist, not an immunologist. Lidophilumab is a humanized monoclonal antibody, binds to the BDCA2 protein. That's the blood dendritic cell antigen on Plasma Cytoid DCS that inhibits them. So back in 2022, New England Journal Medicine published results from a phase two trial called LILAC. I Do guys remember that? I sure as hell don't. And that was like clean, like dedicated. Yeah, three different litophil.

[B]

I think I did.

[D]

I think we looked at doing that study at Pitt, which was probably the main reason why.

[C]

Yeah, I didn't remember when that came out. Seemed like a big deal and I totally off my radar. So the Deep Dive paper basically goes through that exact trial. They didn't redo any trial. They just went back to that Lilac. I think that was the Lilac2 trial. Lilac1 was on systemic lupus. So Lilac2 trial and they looked at some additional skin specific outcomes. So I mean it was a ton of data. I guess I don't want to go through all of it. So go through the first one. So proportion of patients raising classy 50, classy 70 at each time point. And they followed the patients out to week 16. These patients, this is sub Q, they got doses at zero, week 02 that was kind of loading dose and then it was week four, week eight, week 12 and then they followed the patients out to week 16. So looking at Clasi 50, which is the clinically meaningful, this data was already published, but it was only the highest dose, the 450 milligram dose that reached statistical significance at week 16. At week 12, all three doses reached statistical significance compared to placebo. But for whatever reason, and it was weird, the placebo group got better from week 12 to week 16 and it made the other two doses not statistically significant. Whereas the 450 dose was Clasi 70, which is really, really hard in most studies, I don't think even look at this, the 150 and the 450 milligram dose was statistically significantly superior compared to placebo.

[A]

Do you have any sense of like how far this drug is from like being on the market?

[B]

Yeah, so it's in phase three studies right now. And full disclosure, I am a PI on that. One of the, we're a site for that study. But yeah, so I mean they're moving forward, they're in the phase three. You know, obviously they're still gathering data. So there's been no data published on the phase three. But I mean the phase two looked good. And one thing I want to point out was the week four that this drug works fast and they saw a difference at week four, which is exciting.

[C]

So here was my, this is what I was thinking looking at the Clasi. So the figure 1B Clasi 50 and if you look at placebo, placebo like it goes up and up and up and up and up. And as we know like this is not placebo. These patients are on like maintenance. Do you think, like, is it entirely possible that patients say that they're on a stable dose of hydroxychloroquine? Because it had to be stable, it had to be like stable therapy, like a 12 week wash in or something like that. Do you think they enter a trial and they just start being more compliant with her hydroxychloroquine and that's why you see this nice little rise in the placebo from week two to week 16. How, how much of having the patients take their other medications and maybe being more compliant with those medications, do you think that interferes with maybe some of the data?

[B]

I think that's a really good point. And that's something that we talk about in the industry both in for lupus and dermatomyositis is you see a big placebo and as you're correct, it's not really placebo. Right. They're on baseline treatments. I think rarely these patients are on Nothing else. They're almost always on something. So placebo is probably not the right word, but let's just use it because that's what it says in the studies. But there's a big placebo effect in these trials. And I think you bring up a good point. A lot of these patients aren't always very compliant. They've been sick for a long time. They get sick of their medicine. So there, I think there is an element of that. I do think there's a little maybe rater element to, you know, it's subjective that you're rating. Is that deep red, is that red, is that pink? You know, so. And it's a numeric scale and, you know, skin of color is harder to do than light skin. Also, these diseases ebb and flow with the season. And, you know, the clinical trials are enrolling all year, wrong, all year long. So you would think that would level out, but, you know, there is some vulnerability with ebbing and flowing and the autoimmune diseases too.

[A]

And Dr. Patton, on behalf of my good friend Steve Feldman, I've got to give you a shout out for, for blaming it on changes in adherence, which is exactly. Steve, I'm sure would. If you're out there listening, Steve, I'm trying to, trying to channel you. He would fully blame this on, on exactly what you described, that when people are coming in frequently for visits, because he's shown that repeatedly, that when, when people come in for visits regularly, they are much more compliant with anything. And so he, he would certainly be 100% on board with that idea that their back background therapy, they got more compliant with.

[B]

Right?

[C]

And we were always taught during residency, like hydroxychloroquine is not fast acting, right? Like you tell the patients, you may not see a difference, like you may not start to see a difference until you're at least three months in. So, so I wonder if that played into that. Week four, you don't see much but, you know, in the placebo, but it does actually get better at week 16. But in any event, figure 2 shows that a higher proportion of patients receiving Liddy reached clear or almost clear skin. I don't know if any of those are statistically significant. They don't have any little asterisks above the little bars. And the paper says, quote, more participants achieved clear or almost clear skin status at week 16 with lidofilimab 22 than with placebo three. But, like, why percent it like that? There were like 94 patients in the Liddy groups and 32 in the placebo. Like, why would you do absolute numbers? That, that, that bothered me. All right. Some of the supplemental data, percentages of patients with a seven point or greater decrease in the classy scores and like it, you know, statistical significance kind of varied. When you got to the very end of week 16, it was only the 450 milligram dose where you had a statistically significantly higher proportion of patients receipt or that dropped seven points or in the classy A score. So that's another one. Like, if you drop seven points in the classy A, is that like a big deal no matter where you start? Like, are you like, oh, that is a noticeable difference?

[B]

I think so, yes. I think that is a clinically significant amount. Like I said, they're still doing the studies on to have the exact numbers, but just from experience, that can make a difference.

[C]

They, they broke down patients if you had a low classy at baseline, so you had to have at least a classy of 8. But then they broke it up into, well, if you were less than 10, greater than 10 if you had systemic lupus with that or you didn't if you had discoid lupus or not lupus. But like litophilimab kind of numerically did better than placebo and all those groups and just varied in statistical significance. I mean, it just didn't seem like the only one was if you were greater than 10, all of them were statistically, like, it seems to work better for worse disease, which I guess kind of makes sense. But all the other stuff, with or without sle? With or without dle? I. Nothing really jumped out at me as like, here's where it seems to work better.

[D]

That paper where it seemed like the group that did not have dli, maybe their skin did better. So it's sort of like the SCLA type patients did that. I think those numbers.

[C]

Yeah. What did you take away from the. The grouping? I mean, it was small amount of patients, so I think it's a small number.

[D]

I, you know, I don't know. Lauren, do you think SCLE is either easier to treat than DLE or is it easier to score? I mean, it's probably easier.

[B]

It's easier. It's definitely easier to score because you're just judging the erythema and they don't have as much hyperpigmentation kind of within it to make it harder to see the erythema. So I do think it's easier to score. And then you don't have as much damage afterwards. That kind of masks the ERYTHEMA Okay, I will say that. Sorry. That when your score is lower, it's harder to see a difference. So is it actually better for more severe disease or is just the scoring system better to see a difference with higher numbers?

[A]

Is it set up like passy and easy where it's like 10, you know, 0 to 10% of that body area? 10, you know, 11 to 30% is 2 point, like blah, blah, blah.

[B]

No, it's just what the area of the body is. And then what's the most red or most scaly of each. Each of those areas.

[A]

Okay. Because yeah, it's definitely true that easy gets way less sensitive to change at lower bsa. Like, that's one of the. It's like a terrible measure of disease activity if you're, you know, starting with less than 10% BSA. And so, okay, classy is not quite as bad in terms of BSA ness, but it sounds like it might be in terms of severity of redness and those kinds of things. So Patton, what's the safety profile of this stuff? So it should. It should be that it causes herpes infections out the wazoo.

[B]

You know what?

[C]

I don't know. Like that was a sick. I think that's a signal for anifrolumab. I don't know that there was a, an adverse event that was like specifically concerning for lidophilumab. But there was so much stuff going through this. I don't even know if I like focused on that.

[A]

I.

[C]

One of the most interesting tables was in Figure 4 in the Supplemental stuff. And it was like the physician's global impression. So this was like, did the patients get much improved? Moderately improved, slightly unchanged, slightly worse. But which is probably what we do in real life, right? Patients come back and you're like, oh my gosh, you're way better or I think you're a lot better. Look at this before picture or whatever. So it's kind of subjective, but I think that kind of relates to how we practice. So the top two rankings much improved. Moderately improved. All right, so at week 16 for the 50 milligram dose, 41.7 much and moderate improved. For the 150 dose, 60%. For the 450 46.7. And for placebo, 44%. Like it was better than the 50 milligram dose. Really close to the 450. The 150. Just overall that these seem to be just a better responders overall in the whole study. But that really jumped out at me how like physicians global impression is that something where you're like, that's the hardest part to interpret from these studies, or do you really feel like that's a useful sort of metric to use the first time?

[A]

I'm going to jump in first, give Steve Feldman, who, again, one of my favorite guys, has published the three point dynamic global assessment with the AS a. As a outcome measure that he strongly endorses, which is, are you doing better, worse, or the same? Those are the three points of the three point dynamic global assessment. So, yes, that is exactly how we practice. Okay, now. Now I'll shut up. I had to put that out there.

[B]

I think I, you know, I think the FDA for a while is requiring companies to have an iga, which. And then I think now they're starting to go back to less IGA is what I've been hearing. I don't want to speak for the fda, but because I think sometimes it is hard. Unless you're staring at the pictures from last time and staring at the pictures from this time. Sometimes it's hard to know if they're better or worse. If it's. It's just an incremental change.

[A]

Yep. So, Dr. Graham, any side effect issue? So the reason I said they probably should get herpes out the wazoo is that that is whenever interferon is highly relevant in all herpes viruses. Is that actually a really interesting side note? They just showed that patients who get Eczema herpeticum are much more likely to have autoantibodies against interferon. So they're basically neutralizing their own interferon, and that puts them at high risk for Eczema herpeticum. But maybe, maybe it comes from something other than blood plasma, cytoid, whatevers. Yeah. So, Dr. Graham, any. Any side effect issues that you are aware of with this drug?

[B]

There aren't any large side effects. The anafrolumab studies had definitely had herpes signature, and they do recommend the zoster vaccine before anifrolumab.

[A]

Okay. All right, Pat, anything else?

[C]

Like, there's a lot of other tables, but I'm, I'm willing to call it there. I think lidofilimab, like, numerically looks like a better drug. I think a larger study, you probably do start to get statistical significance, but man, like, it's weird. Like the anafrolumab study on systemic lupus. I thought this was the funniest thing. So the first it would. They. They had like a. Lil. No, a tulip. Tulip. One study for anifrolumab and systemic lupus. The Primary endpoint. Placebo did better.

[A]

What?

[C]

Yeah, it was like 40% of placebo versus 36 of anifrolumab met the primary endpoint for SLE. SLE?

[D]

Yeah.

[A]

You even use for an endpoint in SLE, is it like.

[C]

Well, that. That's the difference because.

[B]

Yeah, there's a lot of rheumatology, sleet A or Sleet eye and a couple other scoring systems for R for SLE includes arthritis, siricitis, pleuritis, lupus. There's a lot of stuff in it.

[C]

Yeah, they. They went and did a Tulip 2 trial, and they're like, forget that primary endpoint. Let's do the primary endpoint where the secondary endpoints in the first trial looked good and they redid the study, and that's how they got the approval. That's my understanding of. Okay. The anafromab history. So anything else with all the data in that paper, Dr. Graham, that jumped out at you?

[B]

No, I think you did a good job. There's a lot of data in the paper.

[C]

Yeah, it was.

[A]

I was like, patent, patents.

[B]

I think they're excited about it. You know, like we've said, there's nothing approved for cutaneous lupus. So it's exciting that there's anything that shows that it's helpful.

[A]

Yeah. Yes. So. All right, let's. Let's go on. I got two. First, I want to go over just relatively quickly, so I. Since I don't know how to say it. Do they make it in Iran?

[D]

That would be Iran.

[C]

You follow?

[B]

And they did.

[D]

Not.

[A]

For anybody who's not a longtime listener, I frequently get mocked by Patent and Fares because I can. I don't say it the correct way. Well, say. Say it the right way.

[C]

No, no, I would say here. Yeah, No, I would say you say Iran just fine. You pronounce it like an American does. And there's nothing wrong with that. We don't call France France. Okay, sorry. But it's all right.

[A]

All right, sorry.

[C]

So this.

[A]

This the initial. So this was one of the studies that. That looked at it for cutaneous lupus. This was a retrospective study where they were. They looked at a bunch of patients. And when I say a bunch, like a fair number, I think they had eight, maybe that got treated with it. And whenever you looked at the classy scores in Figure 1C, it was, like, insane. This had to be a 80% drop on average. I mean, these people just did incredibly well. And I think I've. Of this drug. So I've been sitting in on a Few lectures where people have been talking about using this drug in cutaneous lupus patients who have sle. So you're able to get the drug covered and they're like, oh, my gosh, it is like, miraculous how good this stuff is. So I definitely wanted. Since it is like an FDA prescribable drug, if somebody's got sleigh, I figured it's. It's worth talking about. Certainly I have no experience using it. So, like, Dr. Graham, what's your, what is your take on. Because, like, it wasn't. This was like eight patients of data. It's like, sorry, yeah, there's.

[B]

So there's more patients. They went back and looked at the classy scores of the patients in the SLE trial and they looked really good. So we've been using it a lot. So, you know, I. A lot of us that are in room derm clinic, so I do combined room derma clinic. So I'm with the rheumatologists a lot. Any patient who has systemic lupus whose skin is not under control, the first thing we're giving them is anifrolumab. And it works really well. It works really well and it works fast.

[A]

What's his brand name?

[B]

Cefnello. That's easier to say.

[A]

It's not that much easier to say. What's

[B]

a little easier. But yeah, it looked, I mean, in, in, you know, real life practice, it looks, it looks really good. Patients love it. They don't want to get off of it. There is an infectious signature for sure. And so you do have to be careful of that. But patients are really getting better.

[C]

This is going to turn lupus on its head for us because remember how people would have cutaneous lupus and we'd be like, you don't have systemic lupus. Like, stop it, stop worrying now. We're going to be like, I think you also might have systemic lupus. We can get you.

[B]

It's in clinical trial. It's in clinical trials right now for a sub Q version because. So this was the systemic lupus was iv, but they're studying it in sub Q right now for cutaneous lupus. That's in trial.

[C]

I actually read over in Europe, as of December 2025, they approved the sub Q dose and it's. It's 120 milligrams a week, whereas the IV is 300 monthly. Is. Is the sub Q dose different than

[A]

the iv, like, in terms of efficacy?

[C]

No, like dosing it like, you give the IV 300 milligrams once a month. Right. Is that the dosing?

[B]

Yeah.

[C]

Is the. Is the sub Q trial 120 a week?

[B]

I do not know offhand, I'd have to look that up. I don't. I don't know.

[A]

So do people get both herpes and zoster in it? Like, because, so, like, I'm a believer with Jax, everybody who has AD and goes on a jack, I put on Valtrex. Like, I don't care if they get herpes shingles vaccine or not, because I'm way more worried about Eczema herpeticum than I am about shingles. And the shingles vaccine is not going to protect you at all against Eczema herpeticum. So I put everybody on Valacyclovir. Now, I assume that there's not like a lupus or pedicum, so it's not like a disaster if somebody gets a cold sore the way that it is. It can be an atopic derm. But do people get both more frequent herpes things and I guess every. Like. Do people have to get vaccinated for zoster before they can be in the trial?

[B]

The recommendation is to get this zoster vaccine before you start it. Do they have to start the iv?

[A]

So in four trials, since a lot of them are going to be younger than 50, do they have to get. If they haven't been vaccinated, can they be in the trial, or do they have to get vaccinated before they can start?

[B]

That's a good question. I am not a PI on the trial, so I don't know.

[A]

Yeah, I wouldn't know either. But you. And it shouldn't be broadly immunosuppressive, so getting vaccinated while you're on it should be completely fine. Okay, that's useful. So do you. Could you see it as a drug that derms, like normal dermatologists could be using someday, or do you think of it as a drug that's only going to be in academic centers and combined clinics?

[B]

I think that's a good question. I would hope, especially if a sub Q version is approved, that hopefully dermatologists would be comfortable with it, especially if the safety signature continues to, you know, be relatively safe. I think the dermatologists always take a little bit longer to adopt things. Although now with all our shots available for psoriasis and atopic dermatitis, I think we're much quicker to adopt than we were maybe 10 years ago. So I hope so. I hope so. I think, you know, to be determined, but I hope so because I. It. At least the IV version looks really good in the skin, so I'm hoping the sub Q version looks like that's good.

[A]

Okay, Pat. Pat. And what you made me think about is we need to start working on how to coach our patients to go to the rheumatologist and be like, yeah, I get mouth. I don't have any today, but I get mouth sores all the time. And yes, I have my. Oh, my joints, they hurt so much. It's terrible. Like, I'm so fatigued, I can't remember what all the criteria are. But we got to work on coaching them up on what to say when they go to the rheumatologist so they can get on the. The good stuff.

[C]

Yeah. So, Dr. Grant, you may not want to admit to this on air, and you can just, like, plead the fifth if you don't want to say, are. Are you selling these patients on having SLE more than you think you may have done.

[A]

I would totally be like, so if you had get. If you tell me you get this, I can put you on this really great drug, and if you tell me you don't, then I can't put you on it. So do you want to tell me you do get it? Like, that's how I would be asking.

[B]

Yeah, I. You know, I think everyone's different. You know, you can have a positive ANA. You can have a positive ANA and still have just cutaneous lupus.

[A]

But that one to 40 speckled, you've got it.

[B]

You can have arthritis, joint pain. So, you know, I'm not going to speak for other people, but I do

[A]

think, one thing, you know, carefully go through the criteria.

[B]

But I will say, I think if anything, this tells us we need to own cutaneous lupus.

[C]

Right?

[B]

So if patients don't have systemic lupus, again, right now, we have nothing FDA approved. But if we do get things FDA approved for cutaneous lupus, you know, I think the dermatologists really need to be empowered to take. To take care of it.

[A]

Okay. We've talked a lot about therapy for lupus. Anything new in the diagnostic realm? Like, obviously, it's. There's the clinical aspect of diagnosing it. You know, you do a biopsy, you know, we check, you know, double stranded DNA and ANA and like, the stuff I learned in residency 20 years ago, like, dermatomyositis. Now you do all of this testing and we'll talk about. We're going to get to Dramato after this, but anything that, like, I should know about diagnosing Lupus that I don't like know is it still you order the same labs you've always ordered.

[B]

I don't think there's anything. There's not much new things, unfortunately. I think the biggest thing is just recognizing the difference between lupus and dermatomyositis.

[A]

Yeah.

[B]

Because a lot of the dermatopathologists will just say interface and people assume it's lupus.

[A]

Yeah.

[B]

So do a clinical, a good clinical exam. Make sure it's not dermato.

[A]

Okay. So we're going to jump over just one quick paper on dermato and then we're going to talk a little more in general about dermato. So it was a paper looking at a premolast and dermato from a long time ago. This was like, this was published like 10 years ago, I think, or published in 2022. So not 10 years ago. But the trial was done a pretty long time ago. And obviously nobody's ever going to use a premolast for contagious dermatomyositis because you're never going to be able to get it covered. But the takeaway is it worked pretty well. And so based on this. Right. So they had a very good reduction in the Cadassi, the cutaneous. Yes. Okay. CDassy. Okay. Like that's better than Kadazzi. So they had a pretty good reduction in Kadazzi or Cdazzy. And then whenever they stopped the drug, it looked like people got worse again. And so based on this article, I've been using oral reflumelast. And so. Right. I can't go an episode without talking about oral reflumelast. So that has now become my, my go to because I actually take care of a fair amount of amyopathic dermatomyositis patients because they get, they would get referred for patch test clinic because it was a pretty non specific rash. You know, the biopsy for cutaneous dermatit was often like, oh, there's a little spongiosis, a little interface, you know, so people would send it for patch testing and I'd be like, you don't need patch testing, you just, you've got dermatomyositis. And for years I was always using methotrexate and mycophenolate. But I have now moved over to rifluma last as my, my first line for all of these people and it seems to work pretty reliably for me.

[C]

So.

[A]

Dr. Graham, what. So let in general. So first, what are your go to drugs at the moment? In, in normal cutaneous dermato. Not like horrendous. You know, you've got real dermatomyositis and, you know, you're weak and the blah, blah, blah. But like, the people that we as derm see, how are you approaching cutaneous dramato?

[B]

So I think it depends on how, like you said, severe they are. You know, thankfully, we do have one thing that's FDA approved for Dramato, and that's ivig. So I do use a lot of that, especially if they're bad or can't get anything else under control.

[A]

But I do use, like, how good is IVIG for. For the skin aspects of it?

[B]

Okay, good question. It is good. It's not perfect.

[A]

Okay.

[B]

So it can definitely get people better. Sometimes they still have some leftover disease, but it gets them to a place where they can almost. They can tolerate it. It's not always getting them clear. We still use methotrexate, we still use mycophenolate. There's a new phase three. There's a phase three trial that had very good data called repicitinib, which they're hoping to get to the FDA soon. So that hopefully.

[A]

What is it?

[B]

Tick two, jack one.

[A]

Okay.

[B]

Yes. So that's a novel molecule. Yeah. And so that I'm hoping that's going to be, you know, 2026, maybe early 2027 is what the company is saying. So that's exciting, too.

[A]

How nervous do you get with ivig? So my. My take, because I haven't prescribed IVIG since I was a resident, but my takeaway was that, like, you. You can get some hyperviscosity, like, if. If there is some cardiovascular risk with ivig, because when you dump all that protein into their blood, it can get a little thicker or maybe they're like. Like there's an increased risk of heart attacks and strokes and that kind of stuff. Is that. Is that still, like, people think that or you're.

[B]

Yeah. So it's on the label, increased risk of vt. But there's been some studies have been done, both in just dermatomyositis and in patients who are on a jack in dermato. Because that's another one that, you know, people are starting to use jacks off label, and there was not an increased risk of clots being on IVIG versus. Okay, something like prednisone. Right. I mean, like that the cardiovascular events for prednisone and clots on prednisone's up there too.

[A]

So do you. You do you see your. So let's assume that in 2027 at the latest, Tofacitinib is going to go generic and we'll be able to start prescribing tofacitinib for these people because, you know, right now trying to get somebody on a jack for anything other than an approved indication is so hard. Do you see yourself using ToF? If it's easy, if it's generic and cheap and easy to get, do you see yourself using Tofa or, you know, because if, if any of the jacks have a real risk of Mason vte, it's, it's tofa. Like, do you see yourself using it?

[B]

Yeah, I've used it. So yes, the dose, you know, it's dose dependent. So the lower dose has less risk than the higher dose, the 4mg bid. But I have used it because I've had patients who are so bad they're developing calcium stenosis. We can't get them under control. And there have been lots of papers published that toacinib can help. It's not, it hasn't worked for all my patients, but I've had success with a lot of them and so. Yes, but I'm hoping this new brepicitinib will be better than Tofo with less side effect risks. And then some people are using a patacitinib too off label, obviously.

[A]

Just a matter of getting it covered,

[B]

which you can get sponge derm on the biopsy, like.

[A]

That's exactly right. Over overlap addm. Right. It's all, it's all good. So the are your dramato workup at this point? So Dr. Patton has done a few articles over the last year or so about like the scoring systems to determine how likely somebody is to have malignancy. I remain the like, well, the first two years after you got your rash, then we're worried about it. After that we don't care. What is your like, rule of thumb for like deciding how much to work somebody up for malignancy and when they've got cutaneous. Dramatic.

[B]

Yeah. So that, you know, the new paper and the guidelines came out for the international myositis. Is that the one that you review?

[C]

That's what we cover. So intermediate high. Yeah.

[B]

Yeah. And so dermatomyositis was under the high category no matter what. So I do all my, I do all my patients. I do all the cancer screening yearly for three years.

[A]

Three years onset of rash or three years. So say they've had it for.

[B]

Yeah. Onset of rash.

[A]

Yeah, four years. They're like, man, nobody ever figured this out. Now they sent me to you and you're like, oh, you got dermato. Oh, you've had it for four years. Okay, we don't need to worry about like cancer. Like, is that how you approach it?

[B]

I would still probably do at least one time full screening. It would make me feel better just given this data.

[A]

Like you get a full body CT on these.

[B]

I do a full body CT, mammogram, CA125, pelvic ultrasound, PSA, make them get

[A]

a colonoscopy or you just let them poop in a can.

[B]

I try to convince him to do a colonoscopy.

[A]

I'm a believer in the poop.

[B]

Cold blood is on the. I'm fairly certain that's what's on the recommendation.

[A]

Well, like cologuard is right. So I'm, I'm very much a voice. I'm over 50 now, so I'm very much avoiding getting cold colonoscopy. So I poop in a can every three years and mail it to the people who then, you know, say, well, you're okay, but I think that's better than fecal occult blood, but not as good as colonoscopy. But yeah. Do you, so for the antibodies, do you pretty much like, do you guys have your own lab at uab? Do you just send them to Quest and. Because I think they have like that myositis antibody panel that you can just order so that you don't have to remember like the 19 antibodies or something. Like, do you do that in everybody or what do you do in terms of blood work?

[B]

I think that's a good question because if you read the literature, a lot of the, you know, leading researchers in dermatomyositis, all these new antibodies are coming out and profiling them and I think that's really great. So I do do a myositis panel, but I don't wait for it to get started on treatment because sometimes these are sent outs that can take three or four weeks. It's also lab dependent. I think you can get a lot of false negatives. I have a lot of patients who are antibody negative, but they still have it. Right. And is that just that they have an antibody we don't know about yet? Yeah, maybe. So I do do the screening for the myositis panel. There's different companies and there's different differing opinions on which labs are the are better than others and which labs pick up the antibodies better than others do. So no, we don't have the myositis panel. We do that. We Do a send out to Mayo, but then there's a lab in Oklahoma that does a lot of it too.

[A]

And is it still Again, as a resident, I learned that 50% of Dermato patients are ANA negative. So like literally you like, you're like, oh, we're checking aa, we'll check this. And there's nothing serological that you can find in them. And is it still a meaningful number? Like, is it unlike lupus where you're like, look, your ANA is normal, you don't have lupus or at least systemic lupus. Is dermato still something? We're like, a lot of people have dermato and a negative ana. That's like not a rare thing.

[B]

Yes. I don't, I don't. For dermatomyositis. I don't use the labs to if it clinically, they look like they have it.

[A]

Yeah.

[B]

And the biopsy, you know, I, I diagnose them with it.

[A]

What do you think is the most useful clinic? So the, the thing that I always find, like obviously you look at the people's that they're cuticles, but then for me it seems to be the upper back and the outer arms are like when I see that pattern. And they can have it other places too, but for me, upper back kind of outer arms a little bit violaceousy like that, like bells are going off. Dermatomyositis, Dermatomyositis. No matter what else, if their cuticles are fine, they don't have anywhere but just that rash is like my what, what are your like clues that you would tell people? Like this should make you at least really think about dermatomyositis.

[B]

I always teach my residents recalcitrant scalp erythema. That's a good one to pay attention to recalcitment. I mean, you know, we all see a ton of itch on the scalp for several different reasons.

[A]

Yeah.

[B]

But real, you know, violaceous or pink itch. Plaques with itch that just, you know, won't go away. You know, reconsider it as not subderm or contact term, which it could be too. So those should be on your differential. But I think, I think the back rash, the shawl sign, and then if you look at the fingers, a lot of times they do have the go trends papules on the, you know, PCPs and PIPs, dips. Although you know, the traditional teaching is that lupus is interphalangeal and dermatomyositis on the knuckles. But you know, sometimes patients have it all over and you you can't tell, right?

[A]

Heliotrope to me is one of the most over hyped. Like heliotrope to me is now something where I'm like, I. I identify heliotrope after I know they have dermatomyositis. Kind of like you identify the burrows and scabies after you know they have scabies is like the like. But maybe I'm just not good at picking it up. Like, do you think heliotrope is a common thing at all?

[B]

I think that heliotrope can be one of the harder things to diagnose for sure. Especially, you know, I practice in the South. My ladies don't like to not have makeup on.

[A]

I'll tell you anything else that patent affairs that we wanted to get to, Dr. Graham. Anything we haven't talked about that you think we. We should have.

[B]

I think you guys did a great. I think we did a great job.

[A]

Okay, that's that.

[B]

I think so too.

[D]

I think you covered every connective tissue disease, Matt. That was good.

[A]

And I still can't pronounce any of the generic names of the drugs.

[D]

Yeah.

[A]

So I'm right on. All right, Patton, let's get to trivia. So Dr. Graham, we talked about the rules before the show. We got to let Patton finish reading and then it's just the first person to shout out the correct answer. All right, Pat, what's. What's our. What's our topic this week?

[C]

Do you want to guess? Do you want to play your new game?

[A]

I'm gonna. I'm gonna go with my guess. I think that it's going to be something related to wolves for going off of this systemic lupus erythematosis.

[C]

Yeah. Yeah. You got.

[D]

I'm. I guess I'm gonna guess it's related to tissue.

[C]

It's in some way connective tissue disease history. I just read a bunch about the history of connective tissue diseases. It's pretty interesting stuff. I spent way too much time and I don't think these questions are that great, but here we go.

[A]

We'll be the judge of that.

[C]

In 1953, JC she reported the beneficial effects of anti malarials had in treating SLE and RA and what group of people?

[A]

People with malaria.

[D]

People with malaria.

[C]

I knew you were going to say that.

[A]

No,

[D]

Dr. Graham gets it

[A]

far and I both use.

[C]

It was. It was a group of people who were at really, really high risk for malaria. So they were treated prophylactically in countries.

[B]

High risk. African countries?

[C]

No.

[D]

Oh, like Peace Corps volunteers getting closer.

[C]

1953.

[A]

Medical missionaries, Korean soldiers, soldiers going to

[C]

Korea, U. S. Soldiers, World War II. It was a lag time after the war.

[A]

Okay.

[C]

So, yeah, it was crazy. So malaria was horrible. Like, there was one area. This is great. It was called Milne Bay. I don't know if I'm saying that right. The incidence of malaria per year was 4,000 per 1,000 soldiers.

[A]

Every soldier pretty much got malaria four times a year.

[B]

Wow.

[C]

And it wasn't fatal, but it wiped them out. And so there was this huge campaign of, like, wearing, you know, DEET and spraying ddt.

[A]

And one of my great uncles that died of malaria that he got during World War II. I think he was, like. He was all happy because I think he got deployed. I. Obviously, I never knew him. I think he got deployed to, like, Panama or something, and he got malaria and died. And that was. He was like, the only. They had, like, six brothers. He was the only one who died. I think it was something like that.

[C]

Well, apparently a fair number of soldiers. I guess the criteria wasn't as strict. They had autoimmune conditions, and their autoimmune conditions got better when they were taking them.

[A]

Huh. Do we still. Do we have any idea yet how or why they work for Cutaneous?

[C]

For autoimmune disease, they inhibit autoimmunity.

[A]

Doctor. Dr. Graham, do you know if there's any actual answer to what I.

[B]

You know there is, and I know I should be able to rattle it all off, but I don't. All right.

[C]

Number two cells from a laryngeal epidermoid carcinoma are used in what common assay to test for autoimmune disease.

[A]

A.

[C]

A. It's a. N. A. I was first. You were. Do you know I was third. That in the 60s, they actually realized way back then that the Hep 2 cell line was actually contaminated by the HeLa cell line. So it's actually HeLa cells that Henrietta lacks. Cervical cancer line. That's what those hep. Yeah, they. That's what that cell line is.

[B]

Wow.

[D]

Well, that family, they just got a big settlement.

[B]

Where they go.

[C]

Vartis, I think from.

[D]

Was it Novartis?

[A]

All right, that's because you.

[D]

If they're listeners to derms on drugs, go after the A people too.

[B]

Go to quest. They owe you.

[C]

All right, last question. Heinrich Gotron. We spoke of Gotron Papules. We all still use that term. He was a member of the Nazi party. Yeah, I know. Wait a week.

[D]

Leave us on a low note. All right.

[C]

He became head of the Breslau Dermatology Clinic in 1934 for forcing out this man whose name is associated with a cosmetic chemical peel.

[D]

Jessner.

[C]

Yeah.

[A]

Is it Yesner or. Wait, I'm going to answer Yesner.

[C]

Well, we.

[D]

That's probably the man.

[C]

The man from Iran is saying. Yes. Max Jessner. He was forced out because of his Jewish heritage, and Gotron took over his spot.

[B]

I'm surprised. I feel like we've changed a lot of names of things that were named after Nazis, but we haven't changed that one.

[C]

Well, apparently, like, you know, even among Nazis, there were worse Nazis than others. So, like, writer. Writer was bad. Like, he did typhoid studies on prisoners, and that's why. So Writer's disease, that's gone. And Wagner was the other guy. He. He actually got put up on, like, wartime charges. Gotron, it was. He. He got a good job and he actually wasn't that bad of a dude, apparently.

[A]

I remember. I can't remember if it was at OSU or at Pitt when Elston came to give a lecture on connective tissue disease and he was proposing that they be renamed Dirtbag Papules instead of. Instead of. He was ahead of his time. He was ahead of time.

[C]

Hasn't caught on, though. I think Gotron's with us. That's. That's here to stop.

[B]

I don't think Patience would like the name Dirk Bag.

[D]

Yeah, that was hard to get an icy.

[B]

I love Dr. Alston, but I don't think patients would like that name.

[C]

Yeah, not a good. Not a good.

[B]

All right.

[C]

That's all I got.

[A]

All right. That was. That was pretty good stuff, Patton. I mean, the A1 was a little easy. That was a little below you, but otherwise, that was pretty good stuff.

[C]

I think I really wanted to talk about how it's actually hela. I thought that was interesting.

[A]

Okay.

[C]

Okay. It's my own little thing.

[A]

Okay, okay. That's fair. That's fair. Dr. Graham, thank you for joining us this week. And I want to thank all of our listeners for joining us this week. We hope you learned a few things. We hope you laughed once or twice. And mostly we're hoping you're planning to join us next week. And until then, I'm Matt Zyrus.

[C]

I'm Tim Patton.

[D]

And I'm Laura Faris. And we are Derms on Drugs.